This work is aimed at developing an understanding of enzyme mechanisms in relation to the practical design of potent antimetabolites, termed "transition state analogs", which resemble intermediates in the enzyme catalyzed transformation of substrates. Groups of enzymes studied include carbohydrate isomerases, hydrolytic enzymes for carbohydrates, peptides and nucleic acid derivatives, and choline acetylase. Transition state analogs are bound by these enzymes very much more tightly than substrates, and may thus be useful in controlling metabolic processes connected with microbial diseases and neoplastic transformation. BIBLIOGRAPHIC REFERENCES: The Action of Bacterial Cytidine Deaminase on 5, 6-Dihydrocytidine, Ben E. Evans, Gordon N. Mitchell and R. Wolfenden, Biochemistry 14, 621-624 (1975). The Influence of pH on the Interaction of Inhibitors with Triosephosphate Isomerase and Determination of the pKa of the Active Site Carboxyl Group, Fred C. Hartman, Glen C. LaMuraglia, Yasuko Tomozawa and Richard Wolfenden, Biochemistry 14, 5274-5279 (1975).